TRAIL receptor agonist conatumumab with modified FOLFOX6 plus bevacizumab for first-line treatment of metastatic colorectal cancer: A randomized phase 1b/2 trial Journal Article


Authors: Fuchs, C. S.; Fakih, M.; Schwartzberg, L.; Cohn, A. L.; Yee, L.; Dreisbach, L.; Kozloff, M. F.; Hei, Y. J.; Galimi, F.; Pan, Y.; Haddad, V.; Hsu, C. P.; Sabin, A.; Saltz, L.
Article Title: TRAIL receptor agonist conatumumab with modified FOLFOX6 plus bevacizumab for first-line treatment of metastatic colorectal cancer: A randomized phase 1b/2 trial
Abstract: BACKGROUND In patients with previously untreated metastatic colorectal cancer (mCRC), we conducted a phase 1b/randomized phase 2 trial to define the safety, tolerability, and efficacy of mFOLFOX6 plus bevacizumab (mFOLFOX6/bev) with conatumumab, an investigational, fully human monoclonal IgG1 antibody that specifically activates death receptor 5 (DR5). METHODS Twelve patients were enrolled in a phase 1b open-label dose-escalation trial of conatumumab with mFOLFOX6/bev; thereafter, 190 patients were randomized 1:1:1 to receive mFOLFOX6/bev in combination with 2 mg/kg conatumumab, 10 mg/kg conatumumab, or placebo. Therapy cycles were repeated every 2 weeks until disease progression or the occurrence of unacceptable toxicity. RESULTS In phase 1b, conatumumab with mFOLFOX6/bev was tolerated without apparent added toxicity over mFOLFOX6/bev alone. In phase 2, conatumumab with mFOLFOX6/bev did not confer a benefit in progression-free survival when compared with placebo with mFOLFOX6/bev. Toxicity was similar in all treatment arms. Following treatment, similar increases in circulating caspase-3 levels were observed in all arms. CONCLUSIONS Conatumumab with mFOLFOX6/bev did not offer improved efficacy over the same chemotherapy with placebo in first-line treatment of patients with mCRC. These data do not support further development of conatumumab in advanced CRC.
Keywords: bevacizumab; metastatic colorectal cancer; folfox; amg 655; conatumumab; death receptor 5 agonist
Journal Title: Cancer
Volume: 119
Issue: 24
ISSN: 0008-543X
Publisher: Wiley Blackwell  
Date Published: 2013-12-15
Start Page: 4290
End Page: 4298
Language: English
DOI: 10.1002/cncr.28353
PROVIDER: scopus
PUBMED: 24122767
DOI/URL:
Notes: Export Date: 2 January 2014 -- CODEN: CANCA -- Source: Scopus
Altmetric
Citation Impact
BMJ Impact Analytics
MSK Authors
  1. Leonard B Saltz
    791 Saltz